The goal of this study is to obtain a better understanding of the biosynthesis and biological role of the Staphylococcus aureus type 5 capsule (CP5). Cloning and sequencing of the genetic region necessary for CP5 synthesis has allowed for the initial characterization of the proteins involved in capsule production. We have demonstrated that the cap5P and cap50 genes functionally complement mutations in homologous genes involved in Escherichia coli enterobacterial common antigen synthesis, and likely encode the enzymes UDP-G1cNAc 2-epimerase and UDP- ManNAc dehydrogenase, respectively (Appendix 1). Analysis of the in vitro enzymatic activities associated with the purified Cap5P and Cap50 proteins and mutagenesis of the cap5P and cap5O genes will confirm their roles in the CP5 biosynthetic pathway. By developing a mouse model for intranasal S. aureus colonization, we will study the role played by the type 5 capsule in colonization and persistence of S. aureus in the nasal cavity. In future studies, such a model will assist in identifying other factors involved in colonization and potential targets for eliminating S. aureus nasal carriage.